Free Radicals in Neurodegenerative Diseases: Modulation by Palladium α-Lipoic Acid Complex

Abstract

Our research is based on the need for modern medicine to develop a safe and nontoxic product with a wide spectrum of uses. We strongly believe that one of the best ways to achieve this is to have a product that participates actively in most of the roles played by the mitochondria for optimal cellular function. Mitochondria are ubiquitous, and taking care of mitochondria is similar to taking care of all the parts leading to greater achievements than the sum of the parts [Krishnan et. al., 2011]. Oxidative stress is caused by the chemical imbalance between reactive oxygen species (ROS) production and their breakdown by antioxidants. Over-abundance of ROS has been found during neuronal development, as well as in numerous neuropathological conditions. A predominant feature of neuronal injury is the onset of oxidative stress. Oxidative stress and mitochondrial dysfunction have been closely associated in many subcellular, cellular, animal, and human studies of both acute brain injury such as ischemia and stroke and neurodegenerative processes such as Parkinson’s, Alzheimer’s and Huntington’s. While the oxidative stress occurs chronically in Alzheimer’s disease, it is more acute in ischemic reperfusion injury. The consequences of mitochondrial dysfunction include DNA and protein damage, lipid peroxidation, disruption of the mitochondrial permeability transition, Ca2+ homeostasis, and triggering apoptosis. It is essential to have a healthy mitochondria contributing substantially to the physical, mental, and emotional elements needed to support the well being of patients suffering from brain injury or neurodegenerative diseases. Energy metabolism, calcium regulation, and apoptosis-signaling pathways are the major roles of mitochondria. Energy requirements dictate the number of mitochondria in a cell [Beattie, 2002; Nagley et. al., 2010]. Cardiac and skeletal muscles, the brain, and the liver have the most mitochondria because of their high metabolic activities. These cells are also exposed to the most oxidative stress because the source of free radical production is also the mitochondria. Due to low levels of antioxidants in neurons, they are intrinsically illequipped to defend against an increase in oxidative stress. Glial cells including astrocytes play a supplementary role in antioxidant defense of neurons [Higgins et. al., 2010]. Our search for an extremely safe (up to 40 mL/day, 0.037 M aqueous solution) and nontoxic therapeutic agent resulted in the development of a novel redox molecule, “Palladium α-Lipoic Acid Complex” that is active in mitochondrial cellular metabolism and other